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The effect of subcutaneous injections of melatonin, arginine vasotocin, and related peptides on pituitary and plasma levels of luteinizing hormone, follicle-stimulating hormone, and prolactin in castrated adult male rats.

A sc injection of 2 micrograms arginine vasotocin (AVT) administered every 2 h for a 25-h period starting 1 h after castration of adult male rats caused a 43% reduction (P less than 0.05) in plasma levels of LH compared to diluent-treated castrated controls. In Exp 2, a sc injection of 5 micrograms AVT or diluent was administered to intact or acutely castrated male rats every 3 h for 48 h. After AVT administration, both plasma LH (P less than 0.001) and FSH (P less than 0.05) were significantly reduced, with a concomitant increase in pituitary levels of these gonadotropins. Using the same injection regimen in Exp 3, 250 micrograms melatonin had no effect on plasma or pituitary levels of LH in castrated male rats. In the fourth experiment, neither 1 IU arginine vasopressin nor 1 IU oxytocin had an effect on plasma or pituitary levels of LH, whereas 1 IU of AVT significantly lowered plasma levels of LH (P less than 0.05) and prevented the fall in the pituitary level of this gonadotropin (P less than 0.01) when compared to diluent-treated castrated control rats. Oxytocin (1 IU) significantly inhibited (P less than 0.01) plasma levels of FSH and raised plasma levels of PRL (P less than 0.01) in castrated male rats. No effect on plasma titers of PRL were observed after treatment of castrated rats with AVT in Exp 2 or 4. It is concluded that in acutely castrated male rats, AVT could possibly act either on the hypothalamus and/or the pituitary to affect pituitary and plasma levels of gonadotropins.

Animals↗

Acceleration of granulocytic cell recovery in irradiated mice by a single subcutaneous injection of a heat-killed Lactobacillus casei preparation.

Flow cytometric analysis showed that the treatment of irradiated mice with a heat-killed Lactobacillus casei preparation (LC 9018) accelerated the recovery of granulocytic cell populations in peripheral blood, spleen and femur bone marrow. The recovery of the lymphocytic cell population was not accelerated while the recovery of the B-lymphocytic cell population was inhibited. Histological analysis also showed that the LC-9018 treatment markedly enhanced granulopoiesis in the spleen and bone marrow of irradiated mice. The same LC-9018 treatment significantly increased 30-day survival rates of athymic nude mice after lethal whole-body irradiation. The recovery of the granulocytic cell population in peripheral blood of irradiated athymic nude mice was also accelerated by LC-9018 treatment. Our results suggest that LC 9018 protected lethally irradiated mice from bone marrow death by enhancing granulopoiesis rather than lymphopoiesis and that the contribution of activated T lymphocytes to the enhancement of the granulopoiesis was small.

Adjuvants, Immunologic↗

A five day treatment with daily subcutaneous injections of growth hormone-releasing peptide-2 causes response attenuation and does not stimulate insulin-like growth factor-I secretion in healthy young men.

The synthetic hexapeptide growth hormone-releasing peptide (GHRP)-2 specifically stimulates GH release in man. To determine the effects of prolonged treatment and whether response attenuation occurs in man, we administered to nine healthy subjects a daily s.c. injection of 100 microg GHRP-2 over 5 days. Every day blood samples were taken to determine GH, IGF-I, IGF-binding protein (IGFBP)-3 and osteocalcin levels. On days 1,3 and 5, GH was measured at -20,0,20,40,60,90,120 and 180 min using an immunometric and an immunofunctional assay. Mean-/+S.D). peak GH concentrations were 83+/-31, 59+/-22 and 51+/-13 microg/l on days 1, 3 and 5 respectively. Mean+/-S.D. areas under the curve for days 1, 3 and 5 were 6366+/-2514, 3987 +/- 1418 and 3392+/-1215 mU/l per min. Despite the maintained GH release, analysis of variance revealed that significant response attenuation occurred (P < 0.01). Mean serum IGF-I concentration did not increase after a 5 day treatment with GHRP-2. Mean basal levels were 22, 25,23,25,23,24 nmol/l measured on days 1 to 6. However, osteocalcin, another serum marker of GH activity in tissue, increased significantly from 3.2+/-1.0 to 4.2+/-0.4 microg/l (mean+S.D.) (P< 0.01).

Adult↗

Influence of subcutaneous injection of essential fatty acids on the stress-induced modifications of rat platelet aggregation and membrane lipid composition.

Membrane lipids play an important role in the function of blood platelets but the mechanisms by which the lipid composition of the platelet membrane is adjusted remain unclear. It has been shown that stress and poly-unsaturated fatty acids modified the lipid composition of blood plasma and platelet lipids, but very little is known about the effect of stress and fatty acids on membrane platelet lipid composition. The purpose of the present investigation was to study the influence of the essential fatty acids: linoleic, linolenic and arachidonic acids on the composition of the platelet membrane lipids of rats assigned to heat and restraint stress. It was shown that injections of polyunsaturated fatty acids decrease or suppress the stress-induced increase in platelet aggregation, suppress the stress-induced modification of the composition of the platelet membrane lipids and modify the fatty acid composition of the platelet membrane phospholipids.

Animals↗

NMDA receptors mediating Fos expression in rat spinal cord induced by subcutaneous injection of formalin.

AIM: To examine the effects of N-methyl-D-aspartate (NMDA) and non-NMDA receptors on noxious stimulation-induced Fos expression in the rat spinal cord. METHODS: Formalin (2%) was injected s.c. into one hindpaw of the rat. Fos expression was exhibited by immunocytochemical technique. RESULTS: Two hours after s.c. formalin, Fos-like immunoreactive (FLI) neurons were distributed mainly in medial part of the lamina I and the outer lamina II of the ipsilateral dorsal horn. dl-2-Amino-5-phosphonovalerate (APV) administered intrathecally (10 microL, 0.01, 0.1, or 1 g.L-1) before injection of formalin into a hindpaw reduced the number of FLI neurons dose-dependently in the dorsal horn (P < 0.01), while 6,7-dinitroquinoxaline-2, 3(1H,4H)-dione (DNQX) (1 g.L-1) was ineffective. CONCLUSION: NMDA receptor mediated noxious stimulation-induced Fos expression in the rat spinal cord.

2-Amino-5-phosphonovalerate↗

Tumor induction by a single subcutaneous injection of sterigmatocystin in newborn mice.

Sterigmatocystin, a mycotoxin produced by Aspergillus versicolor, Aspergillus sydowi, Aspergillus nidulans, and a species of Bipolaris, was given to newborn BALB/c X DBA/2F1 (hereafter referred to as CD2F1) mice by a single s.c. administration in 1% gelatin suspension. In an acute toxicity study, the maximum tolerated dose of sterigmatocystin was 5 mug/g body weight. In a chronic study, a single s.c. injection of 5, 1, or 0.5 mug/g body weight gave rise to high incidences of lung and liver adenomas when the animals were killed at the end of 1 year. The incidence of both tumors in mice at the dose of 5 mug/g body weight was statistically significant, and the incidences of lung tumor in female mice and of liver tumor in male mice at the dose of 1 mug/g body weight were also statistically significant, compared with tumors in control mice. Other tumors also were induced in treated mice (two malignant lymphomas and one adenoma of the submaxillary gland), in contrast to a zero incidence in vehicle control mice. These results confirm that a small quantity of sterigmatocystin induces tumors of lung and liver and that the dose of sterigmatocystin is related to the incidence of tumors in mice.

Adenoma↗